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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
1999-6-30
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pubmed:abstractText |
The human CD30 receptor is highly overexpressed on the surface of Hodgkin Reed-Sternberg cells and has been shown to be an excellent target for selective immunotherapy using monoclonal antibody-based agents such as immunotoxins. To construct a new recombinant immunotoxin for possible clinical use in patients with Hodgkin's lymphoma, we have chosen the murine anti-CD30 hybridoma Ki-4 to generate a high-affinity Ki-4 single-chain variable fragment (scFv). Hybridoma V-genes were polymerase chain reaction-amplified, assembled, cloned and expressed as a mini-library for display on filamentous phage. Functional Ki-4 scFv were obtained by selection of binding phage on the Hodgkin lymphoma-derived, CD30-expressing cell line L540Cy. The selected recombinant Ki-4 scFv was shown to specifically bind to an overlapping epitope on the CD30 antigen with binding kinetics similar to those of the original antibody. The Ki-4 scFv was subsequently fused to a deletion mutant of Pseudomonas exotoxin A (ETA'). The resulting immunotoxin Ki-4(scFv)-ETA' specifically binds to CD30+ L540Cy cells and inhibits the protein synthesis by 50% at a concentration (IC50) of 43 pM. This recombinant immunotoxin is a promising candidate for further clinical evaluation in patients with Hodgkin's lymphoma or other CD30+ malignancies.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-1310894,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-1358432,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-1384801,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-1748994,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-1908075,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-2152774,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-2170012,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-3041370,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-3087629,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-7110326,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-7530238,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-7591211,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-7591221,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-7689421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-7944335,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-8080817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-8397766,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-8481509,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-8616080,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-8647523,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-8871664,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-8879196,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-8962138,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-9002941,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-9384666,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-9384698,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-9836471,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10376974-9852227
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0007-0920
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
80
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1214-22
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10376974-Antigens, CD30,
pubmed-meshheading:10376974-Bacterial Toxins,
pubmed-meshheading:10376974-Exotoxins,
pubmed-meshheading:10376974-Hodgkin Disease,
pubmed-meshheading:10376974-Humans,
pubmed-meshheading:10376974-Hybridomas,
pubmed-meshheading:10376974-Immunotoxins,
pubmed-meshheading:10376974-Peptide Fragments,
pubmed-meshheading:10376974-Pseudomonas,
pubmed-meshheading:10376974-Recombinant Fusion Proteins,
pubmed-meshheading:10376974-Reed-Sternberg Cells,
pubmed-meshheading:10376974-Tumor Cells, Cultured
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pubmed:year |
1999
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pubmed:articleTitle |
An anti-CD30 single-chain Fv selected by phage display and fused to Pseudomonas exotoxin A (Ki-4(scFv)-ETA') is a potent immunotoxin against a Hodgkin-derived cell line.
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pubmed:affiliation |
Department of Internal Medicine I, University Hospital Cologne, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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